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1.
Anticancer Res ; 39(10): 5811-5820, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570486

RESUMO

BACKGROUND/AIM: This study aimed to investigate the clinical outcomes and role of adjuvant concurrent chemo-radiation therapy (CCRT) compared to adjuvant chemotherapy alone in young patients with gastric cancer (GC) defined as those ≤45 years old versus older patients. PATIENTS AND METHODS: Data were collected from December 2004 to January 2013 on patients with pathologically confirmed, regional lymph node metastasis of GC who had undergone curative D2 resection. RESULTS: During the study period, a total of 1,633 patients (341 young and 1,292 older GC) was investigated. Female sex and diffuse type were more frequent among the younger group, but, lymphatic and venous invasion were less frequent. During the follow-up, there was no difference in recurrence-free survival (RFS; p=0.81), but RFS was significantly higher in young patients with stage II GC (p=0.02). In the younger group, adjusted RFS did not differ according to adjuvant treatment (p=0.98), but the RFS was significantly higher in the older group treated with CCRT than with chemotherapy alone after adjustment for significant prognostic factors (p=0.008). CONCLUSION: Although young patients with GC had different characteristics, their clinical outcomes did not differ from those of the older patients. In the present study performed in curatively D2-resected GC, there was no benefit from adjuvant CCRT over chemotherapy alone among young patients, unlike among the older patients.


Assuntos
Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimiorradioterapia/métodos , Quimioterapia Adjuvante/métodos , Terapia Combinada/métodos , Intervalo Livre de Doença , Feminino , Gastrectomia/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Neoplasias Gástricas/mortalidade
2.
Zhongguo Zhong Yao Za Zhi ; 44(14): 3107-3115, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31602860

RESUMO

The aim of this paper was to investigate the effects of curcumin on the proliferation,migration,invasion and apoptosis of human gastric cancer cells and to explore the potential mechanisms. SGC7901,MKN45 and NCI N87 cells lines were cultured under different concentrations of curcumin( 2. 5,5,10,20,40,80 and 160 µmol·L~(-1)) at different time points( 12,24,48 and 72 h),and the effect of curcumin on cell proliferation was detected by CCK-8 assay. The migration and invasiveness of cells were determined by wound healing and Transwell assays,the apoptosis rate was assessed by flow cytometry,the expression of N-cadherin,E-cadherin,snail1,Wnt3 a,p-ß-catenin,p-LRP6,Bcl-2 and Bax were detected by Western blot,and the enzymatic activity of caspase-3,caspase-8 and caspase-9 was evaluated via caspase kit. RESULTS:: indicated that the proliferation of MKN45 cells was significantly inhibited by curcumin in a dose-and time-dependent manner( IC50= 21. 93 µmol·L~(-1)). Moreover,curcumin could inhibit the migration and invasion of MKN45 cells,downregulate the expression of N-cadherin,snail1,Wnt3 a,p-ß-catenin,p-LRP6 and Bcl-2,and upregulate the expression of E-cadherin and Bax,it could increase the activity of caspase-3,caspase-8,caspase-9 and induce apoptosis as well. The potential mechanism is through inhibiting the Wnt3 a/ß-catenin/EMT pathway,regulating Bcl-2 signaling and caspase pathway,which might provide new potential strategies for gastric cancer treatment.


Assuntos
Curcumina/farmacologia , Neoplasias Gástricas/patologia , Via de Sinalização Wnt , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Humanos , Neoplasias Gástricas/tratamento farmacológico , Proteína Wnt3A/metabolismo , beta Catenina/metabolismo
3.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(10): 977-983, 2019 Oct 25.
Artigo em Chinês | MEDLINE | ID: mdl-31630497

RESUMO

Objective: To explore the value of dual-energy CT-based volumetric iodine-uptake (VIU) in the evaluation of chemotherapy efficacy in advanced gastric cancer. Methods: Inclusion criteria of subjects: (1) without previous systematic therapy; (2) with complete clinical information before and after chemotherapy; (3) without contraindications of chemotherapy. Exclusion criteria of subjects: (1) unfinished duration and times of chemotherapy; (2) unmeasurable primary lesions; (3) poor imaging quality or poor gastric filling. Clinical and image data of 52 patients with advanced gastric cancer who were diagnosed by pathology from gastroscopic biopsy, and needed chemotherapy evaluated by imaging and clinical information in the First Affiliated Hospital of Wenzhou Medical University from February 2017 to February 2018 were collected and analyzed. Of 52 patients, 38 were male and 14 were female with the median age of 65 (31-88) years old. All the patients underwent a dual-energy, dual phase-enhanced CT scanning before chemotherapy and after the third chemotherapy session. The parameters of the lesions measured before and after chemotherapy in portal vein phase were as follows: the maximum diameter (the largest diameter among those measured in the cross-sectional, coronal, and sagittal planes), average CT value (the regions of interest were manually pinpointed under cross-sectional planes with largest diameter of the tumor, which did not include regions less than 2 mm to the edge of the tumor) and VIU (lesion volume × iodine concentration). The change rates of maximum lesion diameter, average CT value and VIU before and after chemotherapy were calculated [(post-chemotherapy parameters-pre-chemotherapy parameters)/ pre-chemotherapy parameters]. The efficacy of chemotherapy was evaluated by RECIST 1.1 (the change of maximum tumor diameter after chemotherapy), Choi (the change of average CT value after chemotherapy) and VIU (the change of VIU after chemotherapy), respectively, which was categorized by complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Patients with CR, PR, and SD were assigned to the effective group, while those with PD were classified as the ineffective group. Paired t - test or Wilcoxon signed ranks test was used to compare the changes of parameters before and after chemotherapy, whereas Spearman correlation analysis and Kappa test were used for the correlation analysis and the consistency test between the three evaluation criteria (Kappa≥0.75 indicated good consistency). Results: After chemotherapy, the average CT value [(74.01±16.75) HU vs. (81.06±15.87) HU, t=2.202, P=0.030] and median VIU (668.53×10(2) µg vs. 272.52×10(2) µg, Z=4.761, P<0.001) decreased significantly, while the difference of the maximum diameter was not statistically significant [(66.71±34.49) mm vs. (78.45±35.62) mm, t=1.708, P=0.091]. The median change rate of VIU (-53.33%) was greater than that of CT values (-5.75%) with significant difference (Z=-5.408, P<0.001). According to the RECIST 1.1 criteria, 47 patients (90.4%, including 19 with PR and 28 with SD) were effective and 5 patients (9.6%) were ineffective. According to the Choi criteria, 45 patients (86.5%, including 37 with PR and 8 with SD) were effective and 7 patients (13.5%) were ineffective. According to the VIU criteria, 46 patients (88.5%, including 41 with PR and 5 with SD) were effective and 6 patients (11.5%) were ineffective. Efficacy comparison among these three criteria showed no significant difference (χ(2)=0.377, P=0.828). As compared to RECIST 1.1 evaluation, the proportion of PR evaluated by Choi and VIU was significantly higher (χ(2)=16.861, P<0.001), whereas the proportion of SD was significantly lower (χ(2)=24.089, P<0.001). There was no significant difference in the proportions of PR and SD between VIU and Choi criteria (χ(2)=0.887, P=0.346). Consistency and correlation analysis showed that the VIU and Choi evaluation criteria presented the highest consistency and correlation (Kappa=0.912, P<0.001; r=0.916, P<0.001). Conclusion: VIU is a feasible parameter for the evaluation of chemotherapy efficacy in advanced gastric cancer, and may be more sensitive than the evaluation criteria based on maximum diameter or change of CT value in the tumor.


Assuntos
Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/tratamento farmacológico , Tomografia Computadorizada por Raios X/métodos , Absorciometria de Fóton , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Radioisótopos do Iodo/farmacologia , Masculino , Pessoa de Meia-Idade , Compostos Radiofarmacêuticos/farmacologia , Indução de Remissão , Neoplasias Gástricas/patologia , Resultado do Tratamento
4.
Medicina (B Aires) ; 79(4): 295-298, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31487252

RESUMO

The infiltration of the bone marrow y non-hematopoietic cells is called myelophthisis. In patients with gastric cancer, this invasion is extremely infrequent and the survival is usually less than three months. We present the case of a 35-year-old man with bone marrow involvement secondary to diffuse gastric carcinoma of signet ring cells.


Assuntos
Anemia Mielopática/diagnóstico , Carcinoma de Células em Anel de Sinete/diagnóstico , Neoplasias Gástricas/diagnóstico , Adulto , Anemia Mielopática/etiologia , Carcinoma de Células em Anel de Sinete/complicações , Carcinoma de Células em Anel de Sinete/tratamento farmacológico , Evolução Fatal , Humanos , Masculino , Neoplasias Gástricas/complicações , Neoplasias Gástricas/tratamento farmacológico
5.
Anticancer Res ; 39(9): 4711-4720, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519570

RESUMO

BACKGROUND/AIM: Dynamics of circulating tumor cells (CTCs) after molecular targeting therapy remain unclear. MATERIALS AND METHODS: We examined changes in CTC numbers and morphology early after targeting therapy in EGFR-mutated PC-9 human lung cancer and HER2-gene amplified GLM-1 gastric cancer mouse CTC models using a cytology-based semi-automated CTC detection platform. RESULTS: Erlotinib and T-DM1 inhibited cell growth mainly by induction of apoptosis in vitro. The number of CTCs detected 5-10 days after targeting therapy in mice was significantly increased compared to CTC numbers before therapy. The increased CTCs after therapy consisted of apoptotic CTCs and viable CTCs. This heterogeneous population of CTCs reflects well the cell population of the primary tumor disrupted by therapy. CONCLUSION: CTCs can be mobilized from the primary tumor due to tissue disruption in acute response to targeting therapy, suggesting potential usefulness of CTC monitoring as a predictor of therapeutic response in the clinical settings.


Assuntos
Amplificação de Genes , Mutação , Células Neoplásicas Circulantes/metabolismo , Receptor ErbB-2/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Biomarcadores , Biomarcadores Tumorais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Receptores ErbB/genética , Cloridrato de Erlotinib/farmacologia , Xenoenxertos , Humanos , Imuno-Histoquímica , Camundongos , Células Neoplásicas Circulantes/patologia , Neoplasias Gástricas/tratamento farmacológico
6.
Anticancer Res ; 39(9): 5195-5201, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519633

RESUMO

BACKGROUND/AIM: Cancer immune therapy by immune checkpoint inhibitors (ICIs) is a promising therapeutic strategy for various cancer types. Among ICIs, anti-programmed cell death protein-1 (PD1) and anti-programmed death-ligand 1 (PD-L1) antibodies have shown a remarkable clinical benefit. The present study aimed to address the functional and clinical significance of serum levels of soluble PD-L1 (sPD-L1) in patients. MATERIALS AND METHODS: A total of 21 patients, 11 with NSCLC, nine with gastric cancer and one with bladder cancer, who underwent anti-PD-1 therapy were evaluated for sPD-L1 concentration by ELISA analyses at diagnosis and after treatment. RESULTS: Pretreatment levels of sPD-L1 in patients who received ICIs were not remarkably correlated with the overall survival of these patients (r=0.3394, p=0.1323). Reduction of plasma sPD-L1 level was significantly correlated with tumor regression in patients administered four cycles of treatment (p<0.05). CONCLUSION: sPD-L1 might be derived and secreted from tumors and might be useful to identify primary responders to ICIs at a relatively early treatment timepoint.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/sangue , Biomarcadores Tumorais , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Neoplasias Gástricas/sangue , Neoplasias Gástricas/patologia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/farmacologia , Antígeno B7-H1/antagonistas & inibidores , Progressão da Doença , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Neoplasias Gástricas/tratamento farmacológico , Resultado do Tratamento
7.
Internist (Berl) ; 60(10): 1043-1058, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31501913

RESUMO

Therapeutic regimens using monoclonal antibodies have been implemented in clinical daily practice for various gastroenterological diseases, for therapeutic strategies in gastrointestinal (GI) oncology, and infectious diseases of the gastrointestinal tract. The main indications remain the therapy of chronic inflammatory bowel disease and in GI oncology. A new field has opened for targeted therapy with monoclonal antibodies of recurrent Clostridium difficile infection. In the nomenclature of monoclonal antibodies, the endings of the substances indicate the production or degree of "humanization" of the respective antibodies ("umab": fully human, recombinant antibody; "ximab": chimeric antibody with variable murine domain). For chronic inflammatory bowel disease, monoclonal antibodies has been developed to interfere with molecular targets of the inflammatory cascade in the underlying pathogenesis (tumor necrosis factor­α, interleukin-12 and -23; α4ß7-integrins). The development of targeted therapies in the treatment of GI malignancies, monoclonal antibodies has been developed to interfere with substantial pathways of proliferation and apoptosis as well as neoplastic vascularization and neovascularization (e.g., vascular endothelial growth factor [VEGF] and VEGF receptor antibodies, epidermal growth factor receptor antibodies, HER2/neu antibodies). In the current review, we provide a summary of the current applications of monoclonal antibodies in the therapeutic treatment of gastroenterological diseases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Gastroenteropatias/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Animais , Anticorpos Monoclonais/farmacologia , Antineoplásicos Imunológicos , Colite Ulcerativa/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Receptores ErbB/efeitos dos fármacos , Gastroenterologia , Humanos , Fatores Imunológicos/farmacologia , Camundongos , Receptores de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Neoplasias Gástricas/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular
8.
Gan To Kagaku Ryoho ; 46(8): 1299-1302, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501374

RESUMO

A 74-year-old man was referred to our hospital because of a gastric tumor. A Borrmann type 2 gastric tumor was found on upper gastrointestinal endoscopy, but tissue biopsy indicated only necrotic tissue and the preoperative diagnosis was difficult. Contrast CT and FDG-PET revealed lymphadenopathy at multiple sites accompanied by high accumulation of FDG in the perigastric lymph nodes, left upper collarbicular fossa, bilateral hilar ganglia, and longitudinal cauda. Because the tumor was strongly suspected to be gastric cancer or malignant lymphoma, distal gastrectomy was performed. The tumor was finally diagnosed as a poorly differentiated adenocarcinoma with multiple lymph node metastasis. S-1 plus cisplatin therapy was administered as first-line chemotherapy, and paclitaxel(PTX)plus ramucirumab(RAM)therapy was administered as secondline chemotherapy. PTX plus RAM therapy was effective, and the patient achieved complete remission(CR), as observed on imaging. However, because adverse events such as numbness in the periphery of the limbs were noted, PTX plus RAM therapy was discontinued per the patient's request. Currently, 13 months since the interruption of treatment, the CR has been maintained, as determined on imaging.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas , Idoso , Anticorpos Monoclonais , Gastrectomia , Humanos , Masculino , Paclitaxel , Neoplasias Gástricas/tratamento farmacológico
9.
Gan To Kagaku Ryoho ; 46(8): 1303-1306, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501375

RESUMO

A 75-year-old woman presented with difficulty in swallowing. Esophagogastroduodenoscopy(EGD)revealed a Borrmann type 3 advanced gastric cardia carcinoma. Computed tomography(CT)revealed three lymph node metastases, and thus, the preoperative diagnosis was cT4aN2M0, cStage ⅢB. However, the patient refused resection, and chemotherapy was initiated. The chemotherapy regimen was sequentially changed based on the macroscopic characteristics of the lesion: S-1 plus CDDP followed by S-1 alone, S-1 plus PTX, and PTX alone. We have continued to follow-upthe lesion using EGD and CT, and have observed the macroscopic characteristics of the advanced gastric carcinoma treated without resection for 7 years.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas , Idoso , Cisplatino , Feminino , Seguimentos , Gastrectomia , Humanos , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Tegafur
10.
Zhonghua Wei Chang Wai Ke Za Zhi ; 22(8): 774-780, 2019 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-31422617

RESUMO

Objective: To investigate the clinical value of laparoscopic peritoneal dialysis catheter implantation in peritoneal chemotherapy for gastric cancer with peritoneal metastasis. Methods: From January 2019 to June 2019, the clinical data of 6 patients diagnosed as gastric cancer with peritoneal metastasis were retrospectively analyzed in the Gastrointestinal Surgery Department of Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine. Five were male and 1 was female. The median age was 69.5 (28-77) years. The median body mass index (BMI) was 22.8 (19.6-23.5). All procedures were performed under general anesthesia with endotracheal intubation. The patient's body position and facility layout in the operating room were consistent with those of laparoscopic gastrectomy. The operator's position: the main surgeon was located on the right side of the patient, the first assistant stood on the left side of the patient, and the scopist stood between the patient's legs. Surgical procedure: (1) trocar location: three abdominal trocars was adopted, with one 12 mm umbilical port for the 30° laparoscope (point A). Location of the other two trocars was dependent on the procedure of exploration or biopsy as well as the two polyester cuff position of the peritoneal dialysis catheter: Usually one 5 mm port in the anterior midline 5 cm inferior to the umbilicus point was selected as point B to ensure that the distal end of the catheter could reach the Douglas pouch. The other 5 mm port was located in the right lower quadrant lateral to the umbilicus to establish the subcutaneous tunnel tract, and the proximal cuff was situated 2 cm away from the desired exit site (point C).(2) exploration of the abdominal cavity: a 30° laparoscope was inserted from 12 mm trocar below the umbilicus to explore the entire peritoneal cavity. The uterus and adnexa should be explored additionally for women. Once peritoneal metastasis was investigated and identified, primary laparoscopic peritoneal dialysis catheter implantation was performed so as to facilitate subsequent peritoneal chemotherapy. Ascites were collected for cytology in patients with ascites. (3) peritoneal dialysis catheter placement: the peritoneal dialysis catheter was introduced into the abdominal cavity from point A. Under the direct vision of laparoscopy, 2-0 absorbable ligature was reserved at the expected fixation point of the proximal cuff (point B) for the final knot closure. Non-traumatic graspers were used to pull the distal cuff of peritoneal dialysis catheter out of the abdominal cavity through point B. The 5-mm trocar was removed simultaneously, and the distal cuff was fixed between bilateral rectus sheaths at the anterior midline port site preperitoneally. To prevent subsequent ascites and chemotherapy fluid extravasation, the reserved crocheted wire was knotted. From point C the subcutaneous tunnel tract was created before the peritoneal steath towards the port site lateral to the umbilicus. Satisfactory catheter irrigation and outflow were then confirmed. Chemotherapy regimen after peritoneal dialysis catheterization: all patients began intraperitoneal chemotherapy on the second day after surgery. On the 1st and 8th day of each 3-weeks cycle, paclitaxel (20 mg/m(2)) was administered through peritoneal dialysis catheter, and paclitaxel (50 mg/m(2)) was injected intravenously. Meanwhile, S-1 was orally administered twice daily at a dose of 80 mg·m(-2)·d(-1) for 14 consecutive days followed by 7-days rest. To observe the patients' intraoperative and postoperative conditions. Results: All the procedures were performed successfully without intraoperative complications or conversion to laparotomy. No 30 day postoperative complications were observed. The median operative time was 33.5 (23-38) min. The median time to first flatus was 1(1-2) days, and the median postoperative hospital stay was 3 (3-4) days, without short-term complications within 30 days postoperatively. The last follow-up was up to July 10, 2019, and the patients were followed for 4(1-6) months. No ascites extravasation was observed and no death occurred in the 6 patients. There was no catheter obstruction or peritoneal fluid extravasation during and after chemotherapy. Conclusion: Laparoscopic peritoneal dialysis catheter implantation was safe and feasible for patients with peritoneal metastasis of gastric cancer. The abdominal exploration, tumor staging and the abdominal chemotherapy device implantation can be completed simultaneously, which could simplify the surgical approach, improve the quality of life for patients and further propose a new direction for the development of abdominal chemotherapy.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Paclitaxel/administração & dosagem , Diálise Peritoneal/instrumentação , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Cateterismo/métodos , Cateteres de Demora , China , Feminino , Humanos , Infusões Intravenosas , Infusões Parenterais , Laparoscopia/métodos , Masculino , Pessoa de Meia-Idade , Diálise Peritoneal/métodos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto Jovem
11.
Medicine (Baltimore) ; 98(31): e16669, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31374043

RESUMO

RATIONALE: With the development of endoscopic technique and the improvement of available accessories, endoscopic therapy became to play an important role in the management of gastrointestinal submucosal tumors (SMTs). PATIENTS CONCERNS: A gastric SMT which was suspected to be gastrointestinal stroma tumor (GIST) was diagnosed in a liver transplant recipient who received transplanted operation 11 months ago. DIAGNOSIS: gastric SMT, post-liver transplantation INTERVENTIONS:: Endoscopic full-thickness resection (EFR) was preformed to remove the tumor. The operation time was 50 minutes and oral immunosuppressant drug was not interrupted in the postoperative period. OUTCOMES: The clinical course was uneventful and slightly elevated liver enzyme was observed on the fourth day after operation. The pathological diagnosis was GIST with complete capsule. LESSONS: Our successful experience showed that EFR is a feasible, safe and efficacious treatment for small (<2 cm) gastric GIST in liver transplant recipients, providing the advantages of little damage, short operative time, stable graft function, without compromising postoperative outcomes.


Assuntos
Gastrectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Neoplasias Gástricas/cirurgia , Transplantados , Adulto , Idoso , Endoscopia/métodos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/patologia , Humanos , Imunossupressores/uso terapêutico , Transplante de Fígado , Masculino , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Resultado do Tratamento
12.
Anticancer Res ; 39(8): 4111-4116, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31366495

RESUMO

BACKGROUND/AIM: We investigated whether the expression of inositol 1, 4, 5-trisphosphate receptor-binding protein released with inositol 1, 4, 5-trisphosphate (IRBIT) in clinical gastric cancer (GC) patients could predict the therapeutic response to postoperative adjuvant chemotherapy. MATERIALS AND METHODS: Immunohistochemistry was used to investigate IRBIT expression in 115 GC patients. To clarify whether IRBIT had a relationship with the therapeutic effects of chemotherapy, we compared two groups - 62 patients treated with postoperative adjuvant chemotherapy and 53 patients treated with postoperative adjuvant chemotherapy. RESULTS: Regarding the postoperative adjuvant chemotherapy-free group, we did not find any statistically significant correlation between clinicopathological features and recurrence regardless of the expression of IRBIT. In contrast, in the group receiving postoperative adjuvant chemotherapy, a significant association was found between IRBIT expression and both overall and disease-free survival. CONCLUSION: IRBIT may be used as a useful predictive marker for chemotherapy.


Assuntos
Biomarcadores Tumorais/genética , Lectinas Tipo C/genética , Proteínas de Membrana/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Idoso , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Fosforilação/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia
13.
Int J Nanomedicine ; 14: 5061-5071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31371947

RESUMO

Background: Photodynamic therapy (PDT) is widely recognized as a promising way to cure cancer. However, the limited tumor homing property of currently available drug delivery systems (DDSs) is the bottleneck for the delivery of photodynamic agents. Purpose: In our study, we decorated silica nanoparticles (SLN) with cell membrane (CM) derived from SGC7901 cells to construct carrier (CM/SLN) which was able to to specifically target the homogenous SGC7901 cells. Materials and methods: Furthermore, the decent drug loading capability of CM/SLN was adopted to load photodynamic agent chlorins e6 (Ce6) to finally construct aDDS suitable for tumor-targeted PDT of gastric cancer. Results: The experimental results suggested that CM/SLN/Ce6 was nano-sized particles with good dispersion and stability in physiological conditions. Moreover, due to the modification of CM,CM/SLN/Ce6 could specifically target the homogenous SGC7901 cells both in vitro and in vivo. Most importantly, further in vivo results demonstrated that the CM/SLN/Ce6 showed a better anticancer outcome compared to SLN/Ce6. Conclusion: CM/SLN/Ce6 might be a promising platform for effective tumor targeted PDT of gastric cancer.


Assuntos
Membrana Celular/patologia , Nanopartículas/química , Fotoquimioterapia , Porfirinas/uso terapêutico , Dióxido de Silício/química , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Peso Corporal/efeitos dos fármacos , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Membrana Celular/efeitos dos fármacos , Coloides , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Humanos , Camundongos , Nanopartículas/ultraestrutura , Tamanho da Partícula , Porfirinas/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Eletricidade Estática , Distribuição Tecidual/efeitos dos fármacos , Carga Tumoral/efeitos dos fármacos
14.
Gene ; 716: 144034, 2019 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-31377317

RESUMO

BACKGROUND: Outcome in adjuvant chemotherapy of gastric cancer (GC) has considerable stage-independent variability, which underscores the need for prognostic or predictive molecular markers. CHAF1A promotes tumor growth while its impact on chemotherapy outcome remains unknown. METHODS: CHAF1A protein expression was measured in independent discovery and validation sets that included 86 and 325 patients respectively who received fluoropyrimidines-based adjuvant chemotherapy after radical gastrectomy. The chemosensitizing effect of CHAF1A knockdown was investigated in vitro. Bioinformatics analysis based on RNA-seq and proteome data from public database was performed to investigate the potential mechanisms and further validation was conducted. RESULTS: In both the discovery and validation sets, CHAF1A expression level was an independent predictor for disease-free survival (HR = 4.25; 95% CI: 2.31-7.79; P < 0.001; and HR = 1.91; 95% CI: 1.03-3.54; P = 0.039, respectively) and overall survival (HR = 3.25; 95% CI: 1.75-6.05; P < 0.001; and HR = 2.42; 95% CI: 1.12-5.20; P = 0.024, respectively) in patients with non-cardia GC but not in those with cardia GC. In GC cells, CHAF1A knockdown significantly decreased the IC50 of 5-FU. Bioinformatics analyses indicated that CHAF1A correlated with folate metabolism and the expression of thymidylate synthetase (TS). Furthermore, CHAF1A knockdown significantly reduced TS expression in GC cells and CHAF1A positively correlated with TS protein expression in tumor tissues. Finally, ten proteins potentially relevant to the regulation of TS expression by CHAF1A were identified using online tools based on RNA-seq and proteome data. CONCLUSIONS: CHAF1A may impact adjuvant chemotherapy outcome of GC by regulating the expression of TS.


Assuntos
Antineoplásicos/uso terapêutico , Chaperonas de Histonas/metabolismo , Pirimidinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Timidilato Sintase/metabolismo , Idoso , Linhagem Celular Tumoral , Quimioterapia Adjuvante , Fator 1 de Modelagem da Cromatina/metabolismo , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos , Feminino , Ácido Fólico/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/enzimologia , Neoplasias Gástricas/mortalidade , Análise de Sobrevida , Timidilato Sintase/genética , Resultado do Tratamento
15.
Cancer Sci ; 110(10): 3145-3156, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31393050

RESUMO

Yes-associated protein (YAP) is a component of the canonical Hippo signaling pathway that is known to play essential roles in modulating organ size, development, and tumorigenesis. Activation or upregulation of YAP1, which contributes to cancer cell survival and chemoresistance, has been verified in different types of human cancers. However, the molecular mechanism of YAP1 upregulation in cancer is still unclear. Here we report that the E3 ubiquitin ligase STUB1 ubiquitinates and destabilizes YAP1, thereby inhibiting cancer cell survival. Low levels of STUB1 expression were correlated with increased protein levels of YAP1 in human gastric cancer cell lines and patient samples. Moreover, we revealed that STUB1 ubiquitinates YAP1 at the K280 site by K48-linked polyubiquitination, which in turn increases YAP1 turnover and promotes cellular chemosensitivity. Overall, our study establishes YAP1 ubiquitination and degradation mediated by the E3 ligase STUB1 as an important regulatory mechanism in gastric cancer, and provides a rationale for potential therapeutic interventions.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/química , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Resistencia a Medicamentos Antineoplásicos , Fosfoproteínas/química , Fosfoproteínas/metabolismo , Neoplasias Gástricas/patologia , Ubiquitina-Proteína Ligases/metabolismo , Animais , Carcinogênese , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Lisina/metabolismo , Camundongos , Transplante de Neoplasias , Estabilidade Proteica , Proteólise , Transdução de Sinais , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Ubiquitinação
16.
Life Sci ; 232: 116615, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31260686

RESUMO

AIM: Gastric cancer (GC) is the fourth most common cancer globally. Bufothionine is a major active constituent of Cinobufacini (Huachansu), which is extracted from the skin and parotid venom gland of the toad Bufo bufo gargarizans Cantor. It exhibits anti-cancer activities in vitro. However, whether bufothionine exerts anti-cancer activities against GC is unknown. This study was designed to evaluate the efficacy of bufothionine in vitro and in vivo. MATERIAL AND METHODS: MKN28 and AGS cells were chosen as cell models to study the anti-cancer effect of bufothionine. Cell viability was determined by CCK-8 assay, while the effect of bufothionine on cell membrane integrity was examined by LDH assay. Cell apoptosis was detected by Hoechst/PI staining and Annexin V-FITC/PI staining followed by flow cytometry analysis. The expression levels of proteins involved were examined using western blotting. I-Traq analysis was conducted to identify the differentially expressed genes in AGS cells following bufothionine treatment. The anti-growth effect of bufothionine was validated in vivo using a GC xenograft model. KEY FINDINGS: The results revealed that bufothionine prevented the growth, destroyed cell membrane and promoted apoptotic cell death of GC cells. iTRAQ analysis revealed thatPIM3 might be a molecular target responsible for the anti-cancer effects of bufothionine. It was also found that PIM3 knockdown significantly augmented the anti-growth and pro-apoptotic effects of bufothionine in GC cells. In contrast, ectopic PIM3 expression markedly dampened the anti-neoplastic activities of bufothionine. The expression of PIM3 was also suppressed by bufothionine treatment in xenograft tumor tissue. SIGNIFICANCE: Bufothionine exhibited anti-cancer activities in vitro and in vivo in GC via downregulating PIM3.


Assuntos
Alcaloides Indólicos/farmacologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Compostos de Quinolínio/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Venenos de Anfíbios/farmacologia , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
17.
Zhongguo Zhong Yao Za Zhi ; 44(13): 2827-2834, 2019 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-31359697

RESUMO

In this paper,the effects of active fractions of Ferula ferulaeoides on the growth and apoptosis of human gastric cancer cell MGC-803 transplantation tumor were systematically studied. The subcutaneous ectopic transplantation tumor model was established in human gastric cancer MGC-803 nude mice by cell suspension implantation method. The anti-tumor rate and organ index were used to evaluate the anti-tumor effect of the active fractions of F. ferulaeoides on the tumor-bearing nude mice. HE staining,TUNEL staining,RT-PCR,Western-blot and ELISA were used for pathological examination,apoptosis observation,and detection of apoptosis-related genes,proteins and cytokines expression. The results showed that as compared with the model group,the low,medium and high doses of the active fraction of F. ferulaeoides had inhibitory effects on xenografts in nude mice,respectively,in a dose-dependent manner; the apoptotic ratio was increased with the increase of drug concentration. As compared with the model group,F. ferulaeoides could down-regulate the expression of survivin mRNA in nude mice,and the protein expression levels of Bax,Bcl-2,caspase-3 and caspase-9 in tumor tissues of nude mice could be increased to different degrees in F. ferulaeoides groups. The contents of IL-10 and TGF-ß1 in plasma of nude mice were decreased in high dose group of F. ferulaeoides active fractions. The results indicated that F. ferulaeoides can significantly inhibit the growth of human gastric cancer MGC-803 subcutaneously transplanted tumor,and its mechanism may be related with down-regulating the expression of survivin mRNA,and up-regulating the expression of apoptosis-related proteins Bax,caspase-3 and caspase-9.


Assuntos
Apoptose , Ferula/química , Extratos Vegetais/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Animais , Caspase 3/metabolismo , Linhagem Celular Tumoral , Citocinas/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína X Associada a bcl-2/metabolismo
18.
Drugs ; 79(12): 1355-1361, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31313098

RESUMO

Camrelizumab (AiRuiKa™), a programmed cell death 1 (PD-1) inhibitor being developed by Jiangsu Hengrui Medicine Co. Ltd, recently received conditional approval in China for the treatment of relapsed or refractory classical Hodgkin lymphoma. The drug is also being investigated as a treatment for various other malignancies, including B cell lymphoma, oesophageal squamous cell carcinoma, gastric/gastroesophageal junction cancer, hepatocellular carcinoma, nasopharyngeal cancer and non-squamous, non-small cell lung cancer. This article summarizes the milestones in the development of camrelizumab leading to this first approval for classical Hodgkin lymphoma.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , China , Aprovação de Drogas , Neoplasias Esofágicas/tratamento farmacológico , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Linfoma de Células B/tratamento farmacológico , Neoplasias Nasofaríngeas/tratamento farmacológico , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Gástricas/tratamento farmacológico
19.
Gene ; 712: 143956, 2019 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-31271843

RESUMO

Gastric cancer represents a common malignancy of digestive tract with high incidence and mortality. Increasing evidence suggests that the growth of gastric tumor cells relies largely on aerobic glycolysis. Currently, many potential anti-cancer candidates are derived from natural products. Here, we evaluated the effects of oleanolic acid (OA), a triterpenoid component widely found in the plants of Oleaceae family, on aerobic glycolysis and proliferation in human MKN-45 and SGC-7901 gastric cancer cells. Our results demonstrated that OA reduced the viability and proliferation of gastric cancer cells and inhibited the expression of cyclin A and cyclin-dependent kinase 2. OA blocked glycolysis in these cells evidenced by decreases in the uptake and consumption of glucose, intracellular lactate levels and extracellular acidification rate. Glycolysis inhibitor 2-deoxy-d-glucose, similar to OA, suppressed gastric cancer cell proliferation. OA also decreased the expression and intracellular activities of glycolysis rate-limiting enzymes hexokinase 2 (HK2) and phosphofructokinase 1 (PFK1). Moreover, OA downregulated the expression of hypoxia inducible factor-1α (HIF-1α) and decreased its nuclear abundance. Upregulation of HIF-1α by deferoxamine rescued OA-inhibited HK2 and PFK1. Furthermore, OA reduced the nuclear abundance of yes-associated protein (YAP) in gastric tumor cells. YAP inhibitor verteporfin, similar to OA, downregulated the expression of HIF-1α and glycolytic enzymes in gastric cancer cells; whereas overexpression of YAP abrogated all these effects of OA. Collectively, inhibition of YAP was responsible for OA blockade of HIF-1α-mediated aerobic glycolysis and proliferation in human gastric tumor cells. OA could be developed as a promising candidate for gastric cancer treatment.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Ácido Oleanólico/farmacologia , Fosfoproteínas/antagonistas & inibidores , Fosfoproteínas/metabolismo , Neoplasias Gástricas/metabolismo , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Ciclo do Ácido Cítrico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glicólise , Humanos , Fosforilação , Transdução de Sinais/efeitos dos fármacos , Estômago/patologia , Neoplasias Gástricas/tratamento farmacológico
20.
Medicine (Baltimore) ; 98(28): e16363, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31305432

RESUMO

RATIONALE: Diffuse large B-cell lymphoma (DLBCL) is the most frequent human immunodeficiency virus (HIV)-related Non-Hodgkin's Lymphoma of the stomach. Although gastrointestinal (GI) bleeding due to primary gastric lymphoma has been previously reported in the literature, there have been no reports of stomach wall involvement of intra-abdominal lymphoma presenting as GI bleeding. PATIENT CONCERNS: We present a rare case of direct invasion of DLBCL to the stomach wall that presented as upper GI bleeding in a patient with HIV. DIAGNOSIS: Upper endoscopy showed a large ulcerofungating mass in the lesser curvature of upper stomach body. The computed tomography scan showed an about 22 × 12 cm sized huge mass that invades into the stomach wall in the abdominal cavity. A diagnosis of DLBCL was established after histological examination. INTERVENTION: The patient was treated with 6 courses of rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). OUTCOMES: The patient achieved a complete response with 6 courses of R-CHOP treatment. No recurrence was observed during the 4-month follow-up period. LESSONS: Because of the high incidence of lymphoma in patients with HIV, if such patients complain of dyspepsia, epigastric soreness, or melena, malignant tumors, such as lymphomas or stomach cancers, should be suspected. As in this patient, doctors should be aware that intra-abdominal lymphoma can invade into the stomach wall and cause bleeding.


Assuntos
Hemorragia Gastrointestinal/etiologia , Infecções por HIV/complicações , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/patologia , Neoplasias Gástricas/complicações , Neoplasias Gástricas/secundário , Diagnóstico Diferencial , Feminino , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/terapia , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico , Trato Gastrointestinal Superior
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